Hepatitis C virus infections most often lead to chronic hepatitis, which can progress to liver cirrhosis and hepatocellular carcinoma. The infection is also associated with steatosis. HCV alters lipid homeostasis. HCV stimulates lipogenesis, impairs mitochondrial -oxidation and lipid export. These altered lipid metabolic activities benefi viral infectious process. Several lipid molecules affect viral replication, assembly, maturation and secretion. In this resubmission of our application, we continue to investigate molecular mechanism(s) associated with HCV-induced alteration of host lipid metabolism. Our current focus will be on effect of HCV gene expression on mitochondrial -oxidation and the mitochondrial dysfunctions associated with chronic hepatitis C. We propose to investigate the effects of HCV gene expression on mitochondrial enzymes involved in lipid metabolism, and mechanisms of clearance of damaged mitochondria via mitophagy. These studies provide a unique insight and open avenues of investigations into HCV-associated liver disease pathogenesis